Abstract
De novo protein design has advanced such that many peptide assemblies and protein structures can be generated predictably and quickly. The drive now is to bring functions to these structures, for example, small-molecule binding and catalysis. The formidable challenge of binding and orienting multiple small molecules to direct chemistry is particularly important for paving the way to new functionalities. To address this, here we describe the design, characterization, and application of small-molecule:peptide ternary complexes in aqueous solution. This uses α-helical barrel (αHB) peptide assemblies, which comprise 5 or more α helices arranged around central channels. These channels are solvent accessible, and their internal dimensions and chemistries can be altered predictably. Thus, αHBs are analogous to “molecular flasks” made in supramolecular, polymer, and materials chemistry. Using Förster resonance energy transfer as a readout, we demonstrate that specific αHBs can accept two different organic dyes, 1,6-diphenyl-1,3,5-hexatriene and Nile red, in close proximity. In addition, two anthracene molecules can be accommodated within an αHB to promote anthracene photodimerization. However, not all ternary complexes are productive, either in energy transfer or photodimerization, illustrating the control that can be exerted by judicious choice and design of the αHB.
Original language | English |
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Pages (from-to) | 3796–3803 |
Journal | Journal of the American Chemical Society |
Volume | 147 |
Issue number | 4 |
Early online date | 15 Jan 2025 |
DOIs | |
Publication status | Published - 29 Jan 2025 |
Externally published | Yes |
Keywords
- peptide barrels
- Confinement
- catalysis
ASJC Scopus subject areas
- Catalysis
- General Chemistry
- Biochemistry
- Colloid and Surface Chemistry